The conformation and movement of Na+ channel inactivation gate peptide in linker between domain III and IV during inactivation by NMR spectroscopy and molecular modeling study.

A model peptide that their sequence corresponds to the linker part between domain III and IV of rat brain type IIA Na+ channel has been synthesized for the conformational affect study corresponded to different gated states of Na+ channel. Nuclear magnetic resonance spectra of local anesthetic (LA) diphenyl drugs, such as phenytoin, in presence of a model peptide in both phosphate buffer and phospholipid bicelles (dimyristotl phosphocholine/dihexanoyl phospholcholine), which micelles serve to mimic the peptide–lipid interactions, have been measured to obtain information of the interactions between selected drugs and model peptide. Molecular modeling is performed to help to provide possible conformational information about the polypeptide LIII–IV that may be critical for recognition and signal transduction of inactivated Na+ channel. The voltage-sensing mechanism of Na+ channel involves the movement of the inactivation particles (Ile, Phe, and Met) in the LIII–IV while binding to S4–S5 intracellular region within DIII and DIV. The movement of LIII–IV making its C-terminal residues, including Glu1492 and Glu1493, may aligned near and stabilize the LAs bound with their receptors. [ABSTRACT FROM AUTHOR]